39. ANTIMETABOLITES AND NUCLEIC ACID METABOLISM 507 



304, 404-406 ]\/[ ore recently it was reported that bromouracil deoxyribonucleo- 

 side can substitute for thymidine in the reproduction of HeLa cells in cul- 

 ture for short periods under conditions in which thymidine is normally 

 required. 407 However, in general, the growth of cells is inhibited by these 

 halogenated derivatives under conditions in which thymine is the limiting 

 factor. 304 408413 It is of interest that chlorouracil was more active than the 

 bromo and iodo derivatives as an inhibitor of the growth of E. coli B/r 

 and that its inhibitory action was partially prevented by uracil as well as 

 by thymine, observations which suggest two sites of action for this com- 

 pound. 411 Similarly,, chlorouridine 414 inhibits the proliferation of Theiler's 

 GD VII virus in chick embryo tissues, an action prevented by uridine. 415 



The deoxyribonucleoside of bromouracil 409, 416 ' 417 has shown greater 

 activity in most bacterial systems than has either the ribonucleoside or 

 free bromouracil and in mammalian systems 418 " 4 - it is the only derivative 

 with striking biological activity, a result which is consistent with the poor 

 utilization of thymine or thymine ribonucleoside in these systems. Sim- 

 ilarly, iododeoxyuridine 421 exhibits a potency as a bacterial inhibitor similar 

 to that of iodouracil; however, unlike the free base, this deoxyribonucleo- 

 side inhibits the growth of several transplantable neoplasms. 421-423 In E. coli 

 the halogenated pyrimidine derivatives create a condition which resembles 

 in many respects nutritional "thymineless" death. 424 



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